DNA polymerase β may be involved in protecting human bronchial epithelial cells from the toxic effects induced by methyl tert-butyl ether exposure

2021 ◽  
pp. 096032712110227
Author(s):  
Z He ◽  
H Xian ◽  
M Tang ◽  
Y Chen ◽  
Z Lian ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Dna Polymerase ◽  
Toxic Effects ◽  
Methyl Tert Butyl Ether ◽  
Human Bronchial Epithelial Cells ◽  
Dna Polymerase Β ◽  
Butyl Ether ◽  
Bronchial Epithelial

Methyl tert-butyl ether (MTBE), a widely used gasoline additive and a ubiquitous environmental pollutant in many countries and regions, can cause various kinds of toxic effects on human health. However, the molecular mechanism underlying its toxic effects remains elusive. The present study aimed to explore the cytotoxicity, DNA damage and oxidative damage effects of MTBE on human bronchial epithelial cells (16HBE) and the possible role of DNA polymerase β (pol-β) in this process. RNA interference (RNAi) was used to obtain pol-β gene knocked-down cells (pol-β−). CCK-8 assay was adopted to analyze the cell viability. Alkaline single-cell gel electrophoresis (SCGE) was performed to detect the DNA damage effects of MTBE. The enzyme activity of GSH-Px, SOD, CAT and the level of MDA were assessed. The data indicated that when treated with MTBE at the concentration exceeding 50 μmol/L and for the time exceeding 24 h, the pol-β− exhibited significantly decreased cell viability and increased DNA damage effects, as compared to the control ( P < 0.05). Furthermore, there was significant difference in the levels of GSH-pX, SOD, CAT and MDA between the pol-β− and the control ( P < 0.05). Our investigation suggests that MTBE can cause obvious cytotoxicity, DNA damage and oxidative damage effects on 16HBE cells. DNA polymerase β may be involved in protecting 16HBE cells from the toxic effects induced by MTBE exposure. These findings provide a novel insight into the molecular mechanism underlying the toxic effects of MTBE on human cells.

DNA polymerase β of Leishmania donovani is important for infectivity and it protects the parasite against oxidative damage

2019 ◽  
Vol 124 ◽  
pp. 291-303 ◽  
Author(s):  
Mohd. Imran Khan ◽  
Anshul Mishra ◽  
Pravin K. Jha ◽  
Kumar Abhishek ◽  
Rachna Chaba ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Dna Polymerase ◽  
Leishmania Donovani ◽  
Dna Polymerase Β

scholarly journals Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 225 ◽  
Author(s):  
Zhongliang Jiang ◽  
Yanhao Lai ◽  
Jill M. Beaver ◽  
Pawlos S. Tsegay ◽  
Ming-Lang Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Dna Damage ◽  
Dna Polymerase ◽  
Dna Methyltransferase ◽  
Oxidative Dna Damage ◽  
De Novo ◽  
Brca1 Gene ◽  
Methylation Pattern ◽  
Dna Polymerase Β

DNA damage and base excision repair (BER) are actively involved in the modulation of DNA methylation and demethylation. However, the underlying molecular mechanisms remain unclear. In this study, we seek to understand the mechanisms by exploring the effects of oxidative DNA damage on the DNA methylation pattern of the tumor suppressor breast cancer 1 (BRCA1) gene in the human embryonic kidney (HEK) HEK293H cells. We found that oxidative DNA damage simultaneously induced DNA demethylation and generation of new methylation sites at the CpGs located at the promoter and transcribed regions of the gene ranging from −189 to +27 in human cells. We demonstrated that DNA damage-induced demethylation was mediated by nucleotide misincorporation by DNA polymerase β (pol β). Surprisingly, we found that the generation of new DNA methylation sites was mediated by coordination between pol β and the de novo DNA methyltransferase, DNA methyltransferase 3b (DNMT3b), through the interaction between the two enzymes in the promoter and encoding regions of the BRCA1 gene. Our study provides the first evidence that oxidative DNA damage can cause dynamic changes in DNA methylation in the BRCA1 gene through the crosstalk between BER and de novo DNA methylation.

scholarly journals Oxidative DNA Damage Defense Systems in Avoidance of Stationary-Phase Mutagenesis in Pseudomonas putida

2007 ◽  
Vol 189 (15) ◽  
pp. 5504-5514 ◽  
Author(s):  
Signe Saumaa ◽  
Andres Tover ◽  
Mariliis Tark ◽  
Radi Tegova ◽  
Maia Kivisaar
Keyword(s):  
Dna Damage ◽  
Oxidative Damage ◽  
Stationary Phase ◽  
Pseudomonas Putida ◽  
Dna Polymerase ◽  
Oxidative Dna Damage ◽  
Oxidation Products ◽  
Base Substitution ◽  
Repair Enzymes ◽  
Starvation Conditions

ABSTRACT Oxidative damage of DNA is a source of mutation in living cells. Although all organisms have evolved mechanisms of defense against oxidative damage, little is known about these mechanisms in nonenteric bacteria, including pseudomonads. Here we have studied the involvement of oxidized guanine (GO) repair enzymes and DNA-protecting enzyme Dps in the avoidance of mutations in starving Pseudomonas putida. Additionally, we examined possible connections between the oxidative damage of DNA and involvement of the error-prone DNA polymerase (Pol)V homologue RulAB in stationary-phase mutagenesis in P. putida. Our results demonstrated that the GO repair enzymes MutY, MutM, and MutT are involved in the prevention of base substitution mutations in carbon-starved P. putida. Interestingly, the antimutator effect of MutT was dependent on the growth phase of bacteria. Although the lack of MutT caused a strong mutator phenotype under carbon starvation conditions for bacteria, only a twofold increased effect on the frequency of mutations was observed for growing bacteria. This indicates that MutT has a backup system which efficiently complements the absence of this enzyme in actively growing cells. The knockout of MutM affected only the spectrum of mutations but did not change mutation frequency. Dps is known to protect DNA from oxidative damage. We found that dps-defective P. putida cells were more sensitive to sudden exposure to hydrogen peroxide than wild-type cells. At the same time, the absence of Dps did not affect the accumulation of mutations in populations of starved bacteria. Thus, it is possible that the protective role of Dps becomes essential for genome integrity only when bacteria are exposed to exogenous agents that lead to oxidative DNA damage but not under physiological conditions. Introduction of the Y family DNA polymerase PolV homologue rulAB into P. putida increased the proportion of A-to-C and A-to-G base substitutions among mutations, which occurred under starvation conditions. Since PolV is known to perform translesion synthesis past damaged bases in DNA (e.g., some oxidized forms of adenine), our results may imply that adenine oxidation products are also an important source of mutation in starving bacteria.

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